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Paradoxical resistance to high fat diet-induced obesity and altered macrophage polarization in mineralocorticoid receptor overexpressing mice.: MR overexpression and adipocyte differentiation

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HAL Id: inserm-00911857

https://www.hal.inserm.fr/inserm-00911857

Submitted on 30 Nov 2013

HAL is a multi-disciplinary open access archive for the deposit and dissemination of sci-entific research documents, whether they are pub-lished or not. The documents may come from

L’archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d’enseignement et de

Paradoxical resistance to high fat diet-induced obesity

and altered macrophage polarization in

mineralocorticoid receptor overexpressing mice.

Emmanuelle Kuhn, Christine Bourgeois, Vixra Keo, Say Viengchareun,

Adeline Muscat, Geri Meduri, Damien Le Menuet, Bruno Fève, Marc Lombes

To cite this version:

Emmanuelle Kuhn, Christine Bourgeois, Vixra Keo, Say Viengchareun, Adeline Muscat, et al.. Paradoxical resistance to high fat diet-induced obesity and altered macrophage polarization in mineralocorticoid receptor overexpressing mice.: MR overexpression and adipocyte differentiation. AJP - Endocrinology and Metabolism, American Physiological Society, 2014, 306 (1), pp.E75-90. �10.1152/ajpendo.00323.2013�. �inserm-00911857�

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A

170 130 100 55 WT Tg 0 0.5 1 1.5 2 2.5 3 3.5 4 M R /α-tu bu lin

B

0 0.2 0.4 0.6 0.8 1 1.2 1.4 R el at iv e Ex pr es si on (m M R /1 8S )

mMR

WT HFD

Tg HFD

0 0.2 0.4 0.6 0.8 1 1.2 R el at iv e Ex pr es si on (h M R /1 8S )

hMR

***

*

MR α-tubulin kDa

Adipose tissue

Isolated Adipocytes

Adipose tissue

0 0.2 0.4 0.6 0.8 1 1.2 1.4

D

E

C

hMR

***

WT Tg WT Tg WT Tg Tg WT R el at iv e Ex pr es si on (h M R /1 8S )

Figure 1

(3)

MR

+

preadipocyte

adipocyte

In Vitro/Ex vivo

macrophage

In Vivo

MR

M1-like macrophages

Inflammation

M2-like macrophages

Alternative activation

MR

(4)

A

B

Basal Medium Control Medium

CM WT CM Tg

C

0 0.2 0.4 0.6 0.8 1.0 1.2 Basal

Medium MediumControl WT CM Tg CM

R el at iv e ex pr es si on (P P A R γ2 /1 8S ) Basal Medium Control Medium WT CM Tg CM

***

***

p=0.08

PPARγ2

0 0.2 0.4 0.6 0.8 1.0 1.2 Basal

Medium MediumControl

R el at iv e E xp re ss io n (F A S /1 8S )

*

***

***

FAS

WT CM Tg CM

(5)

A

x10 x10 x40 x40 WT Tg 0 2 4 6 8 +++ ++ + _ nu m be r of a ni m als (-) (+++) +_

B

0 0.2 0.4 0.6 0.8 1 1.2 R el at iv e ex pr es si on F4 /8 0/ 18 S 0 0.5 1 1.5 R el at iv e ex pr es si on (h M R /1 8S )

***

F4/80

hMR

WT Tg WT Tg WT Tg

C

*

0 5 10 15 20 WT Tg

Gonadal SVF

FSC F4/80

D

0% 25% 50% 75% 100% WT Tg CD11c+ DP CD206+ DN CD11c CD 206 CD11c WT Tg CD206+ CD11c+ DP CD206+ CD11c+ DP C D20 6

E

0 0.2 0.4 0.6 0.8 1.0 R el at iv e ex pr es si on

F4/80

***

***

‡‡‡ ‡‡‡ 0 0.1 0.2 0.3 0.4

CD206

***

**

0 0.05 0.10 0.15 0.20 0.25 0.30

CD11c

***

** ‡‡‡ ‡‡‡ SC HFD SC HFD SC HFD WT Tg WT Tg WT Tg WT Tg WT Tg WT Tg WT Tg F4/80 expressing cells (%) NS 0 2 4 6 8 10 12 14 16 F4 /8 0 ex pr es si ng ce lls (% )

Spleen

**

NS WT Tg WT Tg HFD SC HFD

(6)

R el at iv e Ex pr es si on (mMR/18S) 0 0.5 1.0 1.5 2.0 2.5 R el at iv e Ex pr es si on (P PA R γ2 /1 8S )

PPARγ2

0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0

mMR

WT

Tg

WT Tg WI WP WG Basal Condition Differentiation Cocktail

A

B

C

**

**

*

WI WP WG WI WP WG

Figure 7

(7)

0 0.2 0.4 0.6 0.8 1 1.2 R el at iv e ex pr es si on (P P A R γ2 /1 8S )

PPARγ2

WT

0 0.2 0.4 0.6 0.8 1 1.2 R el at iv e ex pr es si on (G R /1 8S )

GR

0 0.2 0.4 0.6 0.8 1 1.2 R el at iv e ex pr es si on (1 H S D 1/ 18 S )

11βHSD1

0 0.2 0.4 0.6 0.8 1 1.2 0 0.2 0.4 0.6 0.8 1 1.2

*

*

0 0.2 0.4 0.6 0.8 1 1.2

***

*

**

SC

Tg

WT

HFD

A

B

C

D

E

F

Tg

WT

WT

WT

WT

WT

Tg

Tg

Tg

Tg

Tg

R el at iv e ex pr es si on (P P A R γ2 /1 8S ) R el at iv e ex pr es si on (G R /1 8S ) R el at iv e ex pr es si on (1 H S D 1/ 18 S )

(8)

A

0 2 4 6 8 10 12 14 16 18 % a di po cy te s pe r cl as s adipocyte surface (x103µm2)

WT HFD

Tg HFD

0 10 20 30 40 50 60 70 80 % a di po cy te p er c la ss

Distribution of adipocyte surface

WT SC

Tg SC

30

B

p<0.0001 p<0.0001

Figure 5

100µm x10 x10 x10

WT

Tg

SC

HFD

(9)

0 50 100 150 200 250 300 350 400 0 15 30 45 60 90 120 G ly ce m ia (m g/ dl ) Time (min)

WT HFD

Tg HFD

A

0 20 40 60 80 100 120 0 15 30 45 60 90 120 % o f g ly ce m ia a t T 0 Time (min)

WT HFD

Tg HFD

B

*

**

**

C

0 5 10 15 20 25 30 35 WT HFD Tg HFD AUC OGTT

*

(10)

0 0.1 0.2 0.3 0.40.5 0.6 0.7 0.80.9 Weight (g )

Perirenal AT

WT HFD

Tg HFD

*** 0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 Weight (g )

Gonadal AT

** 0 0.2 0.4 0.6 0.8 1.01.2 1.4 1.6 1.82.0 Weight (g )

Inguinal AT

*** 0 0.05 0.10 0.15 0.20 0.25 0.30 Weight (g )

Brown AT

A

B

C

D

Figure 3

(11)

A

B

*** *** 20 22 24 26 28 30 32 0 2 4 6 8 10 12 14 W ei gh t ( g) Weeks

WT SC

Tg SC

20 25 30 35 40 45 50 55 60 0 5 7 9 11 13 15 W ei gh t ( g) Weeks

WT HFD

Tg HFD

0 20 40 60 80 100 % o f b od y w ei gh t g ai n HFD SC WT Tg

C

*** ‡‡‡ ‡‡

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